What is the role of CAR T-cell therapy in the treatment of non-Hodgkin lymphoma (NHL)?

Updated: Feb 25, 2021
  • Author: Sanjay Vinjamaram, MD, MPH; Chief Editor: Emmanuel C Besa, MD  more...
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Answer

Chimeric antigen receptor (CAR) T-cell therapy utilizes each patient’s own T cells, extracted by leukapheresis. The T cells are sent to a processing facility, where they are genetically engineered with CD19 receptors that seek out cancer cells; the T-cell population is then expanded and infused back into the patient, who has undergone conditioning chemotherapy in preparation for the infusion.

In October 2017, FDA approved axicabtagene ciloleucel (Yescarta) for treatment of large B-cell lymphoma after at least two other kinds of therapy have failed. Approved uses include diffuse large B-cell lymphoma (DLBCL), primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma. Axicabtagene ciloleucel is not indicated for the treatment of patients with primary central nervous system lymphoma. [62]

Approval was based on the primary results from the ZUMA-1 study, an open-label, multicenter trial enrolling 111 patients from 22 institutions. Patients in ZUMA-1 received the target dose of axicabtagene ciloleucel (2 x 106 cells/kg) after low-dose conditioning with cyclophosphamide and fludarabine for 3 days. Two-year follow-up data from ZUMA-1 included the following [63] :

  • Objective responses were seen in 83% of patients; complete responses were seen in 58%.
  • Median duration of response was 11.1 months (4.2months to not estimable).
  • Median overall survival was not reached; median progression-free survival was 5.9 months.
  • Grade 3 or worse serious adverse events occurred in 48% of patients, including grade 3 or worse cytokine release syndrome occurred in 11% and grade 3 or worse neurological events in 32%. 

For more information, see Cancer Immunotherapy with Chimeric Antigen Receptor (CAR) T-Cells

 


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